Comparison of anti-interleukin-5 therapies in patients with severe asthma: global and indirect meta-analyses of randomized placebo-controlled trials.

Inconsistent results have been reported regarding IL-5 blockade treatment in asthma. There were no direct between-treatment comparisons. Only differences between each drug and placebo were studied. We identified all RCTs with anti-IL5 treatments for patients with asthma over the 1990-September 2015 period. RCTs were searched on Medline, Cochrane and Embase. At least 50 patients were enrolled in each study. Outcomes considered were exacerbation rate reduction, FEV1 changes, ACQ-5 improvement, adverse events and serious adverse events. A global meta-analysis was first conducted followed by an indirect comparison of each IL-5-targeting drug: benralizumab, reslizumab and mepolizumab. Further eosinophilic subgroup analysis and sensitivity analysis were also conducted in case of heterogeneity. Ten trials involving 3421 patients were eligible for meta-analysis. IL-5 blockade significantly reduced annual exacerbation rates vs. placebo by 40% [29-50] (P < 0.01, I2 = 0.61). ACQ-5 was significantly improved vs. placebo but below the recognized MCID level (-0.31 [-0.41, -0.21], P < 0.01, I2 = 0.11). FEV1 changes from baseline were improved vs. placebo by 0.09 L [0.05-0.12] (P < 0.01, I2 = 0.28). The subgroup analysis identified a slight additional improvement in mean treatment effects in eosinophilic (> 300 mm3 /L) patients with severe asthma. Similar patterns and rates of adverse events and severe adverse events were reported with the three drugs. The data interpretations were not affected by the sensitivity analysis. IL-5 blockade appears to be a relevant treatment strategy to improve severe asthma management, particularly for eosinophilic patients. No clear superiority appeared between the drugs when appropriate doses were compared.